| 1. |
- Andrén, Lennart, 1946, et al.
(författare)
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Diltiazem in hypertensive patients with type II diabetes mellitus.
- 1988
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 0002-9149. ; 62:11
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-three patients with essential hypertension and diabetes mellitus type II were treated with the calcium antagonist diltiazem (120 to 180 mg twice daily). The mean dose was 307 mg/day. The study was a double-blind, placebo-controlled, crossover design. All measurements were performed 12 to 14 hours after drug intake. Blood pressure, heart rate and forearm blood flow were measured noninvasively. Platelet function was studied by measuring adenosine diphosphate-induced platelet aggregation and the platelet specific proteins, beta thromboglobulin and platelet factor 4. Thromboxane B2 formation in serum and the plasma concentration of diltiazem and its metabolites N-demethyldiltiazem, deacetyldiltiazem and N-demethyldeacetyldiltiazem were measured both during placebo and diltiazem treatment. Diabetic control was evaluated by following HbA1C, fasting blood glucose and urinary glucose. Diltiazem reduced both systolic and diastolic (supine and standing) blood pressure significantly. Forearm blood flow was significantly increased by 32%, p less than 0.05. Supine heart rate decreased significantly, while no such change was seen in the standing position. No significant changes were observed in platelet function during diltiazem treatment. There was no relation between the observed blood pressure reduction and the plasma concentration of diltiazem or its metabolites. A positive correlation between the change in heart rate and the metabolite N-demethyldeacetyldiltiazem was observed (r = 0.647, p = 0.005). Three patients were excluded during diltiazem treatment (skin exanthema, headache and atrial fibrillation) and 1 during placebo treatment (angina pectoris). No negative effect on diabetes control was observed. Thus, diltiazem could be used for treatment of hypertension in diabetic patients.
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| 2. |
- Höglund, P, et al.
(författare)
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Antiarrhythmic effect of amperozide, a novel psychotropic compound with class III antiarrhythmic properties, on digoxin-induced arrhythmias in the guinea-pig
- 1986
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Ingår i: Journal of Pharmacy and Pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 38:11, s. 3-861
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Tidskriftsartikel (refereegranskat)abstract
- Amperozide is a novel psychotropic compound with specific effect in limbic brain areas. Preliminary findings have also indicated an antiarrhythmic effect in-vitro. Injections of saline, amperozide, melperone, thioridazine, bretylium or lignocaine, were given i.p. to anaesthetized guinea-pigs, which 10 min later were given digoxin s.c. to induce arrhythmia. In a series of control experiments none of these compounds caused arrhythmia in combination with the vehicle of digoxin. The time to arrhythmia was significantly prolonged after treatment with amperozide, melperone and bretylium compared with saline, but there were no differences between the treatments. The digoxin concentrations in plasma at death varied considerably within the groups and no statistical significance was found.
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| 3. |
- Höglund, P, et al.
(författare)
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Interaction between isoniazid and theophylline
- 1987
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Ingår i: European Journal of Respiratory Diseases. - 0106-4339. ; 70:2, s. 6-110
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic interactions between theophylline and several other drugs have been described in a number of studies. They may be of importance because of the narrow therapeutic range of theophylline. A significant risk for interactions has been considered to exist only with drugs metabolized by oxidative enzyme systems, and thus is not expected to occur with isoniazid. However, an increased clearance of theophylline with oral isoniazid medication has been reported. On the other hand, we found a significant increase in plasma levels of intravenously infused theophylline, and a corresponding decrease in plasma clearance of theophylline, when isoniazid was administered orally, compared to similar infusions in these individuals without concomitant isoniazid medication. The effect was seen irrespective of acetylator status. In five of the seven subjects an increase of isoniazid half-life and AUC was seen with theophylline, but this increase was not statistically significant.
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| 4. |
- Höglund, P, et al.
(författare)
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Liquid chromatographic determination of diltiazem and its metabolites using trans isomers as internal standards, with dynamic modification of the solid phase by addition of an amine to the mobile phase
- 1987
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Ingår i: Journal of Chromatography. B. - 0378-4347. ; 414:1, s. 20-109
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Tidskriftsartikel (refereegranskat)abstract
- A selective and sensitive reversed-phase high-performance liquid chromatographic method for simultaneous analysis of diltiazem and its five metabolites known to occur in man is presented. Different C18 columns are compared. The influences of organic co-solvent, pH, ionic strength and the addition of various amines are studied. The use of trans-diltiazem as internal standard is advocated. UV detection at 237 nm is used for plasma analyses. The possibilities of electrochemical detection are also discussed. Before solvent extraction, plasma samples are saturated with sodium chloride and made alkaline. Triethylamine is also added. The use of the method in pharmacokinetic applications is exemplified.
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| 5. |
- Paulsen, Otto, et al.
(författare)
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No interaction between H2 blockers and isoniazid
- 1986
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Ingår i: European Journal of Respiratory Diseases. - 0106-4339. ; 68:4, s. 90-286
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Tidskriftsartikel (refereegranskat)abstract
- Antacids and anticholinergic drugs may delay gastric emptying and cause reduced absorption of isoniazid, but the influence of reduced gastric acidity has not been determined. In the present investigation, the influence of cimetidine and ranitidine on uptake and elimination of isoniazid was determined in six male and seven female healthy volunteers. The group comprised five rapid and eight slow acetylators, similar to the proportions in the general population. H2 blockers did not delay or reduce uptake of isoniazid, which thus seemed to be pH independent. Neither the acetylation of isoniazid nor the oxidative metabolism of acetylated isoniazid appeared to be affected by cimetidine or ranitidine.
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| 6. |
- Paulsen, Otto, et al.
(författare)
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Pharmacokinetic comparison of two models of endocarditis prophylaxis with amoxycillin
- 1989
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548. ; 21:6, s. 73-669
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Tidskriftsartikel (refereegranskat)abstract
- From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in a single dose, it has been deduced that serum concentrations above 0.12 mg/l should be maintained for at least 10 h after antibiotic administration. Since concentrations above this level are reported to occur following an oral dose of 3 g of amoxycillin, this doses for prophylaxis has become widely accepted in USA and the UK, and presently also in Sweden. Nevertheless, in individuals who cannot tolerate a high single dose of amoxycillin, there is need for an alternative dosage regimen. In the present study, we have compared the pharmacokinetics in 12 healthy volunteers, of a single dose of 3 g of amoxycillin with those of 1 g as single dose or combined with 1 g of probenecid. The combination resulted in an AUC twice as large as that achieved after 1 g of amoxycillin, and was slightly, but not significantly, larger than that after 3 g. However, amoxycillin concentrations above 0.12 mg/l were sustained for almost 14 h with the combination as compared to 10.4 hours following 3 g of amoxycillin only (p less than 0.001). Thus, the combination should be a convenient alternative in patients unable to tolerate a higher oral dose of amoxycillin, and in situations when an antibacterial effect of longer duration is desired.
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| 7. |
- Paulsen, Otto, et al.
(författare)
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The interaction of erythromycin with theophylline
- 1987
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Ingår i: European Journal of Clinical Pharmacology. - 0031-6970. ; 32:5, s. 8-493
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the interaction of erythromycin with theophylline. We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg X kg-1) over 1 h, followed by a maintenance infusion (0.5 mg X kg-1 X h-1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion. Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant. Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication. We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.
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| 8. |
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